Gastrointestinal Cancer

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

In the last 10 years, clinical outcomes have improved for patients with unresectable hepatocellular carcinoma (uHCC). The cancer generally comes with chronic liver inflammation, and liver cirrhosis is present in up to 80% of cases. The level of liver dysfunction helps determine the prognosis, but it also may affect the safety of delivering anticancer treatment.

Clinical trials that have tested systemic immunotherapies have excluded patients who don’t fall into the Child-Pugh class A criteria (CP-A) for liver disease, which is the least severe of the Child-Pugh classes A-C. Therefore, there has been much debate about whether patients who have more liver disease (moderate liver dysfunction) and fit under CP-B criteria, instead of CP-A, should be treated with immune checkpoint inhibitor (ICI) therapy or best supportive care (BSC).

A new study, led by Claudia Angela Maria Fulgenzi, MD, with the Department of Surgery and Cancer at the Imperial College London, England, published in JAMA Oncology on July 18, uses an alternative way to compare outcomes following two different paths of care for uHCC patients with moderate liver dysfunction.
 

How was the study done and what did the investigators find?

Researchers performed a retrospective, multicenter, international clinical case series of patients treated in routine practice in tertiary care centers across Europe, the United States, and Asia. They compared data from uHCC patients with CP-B who were receiving first-line ICI-based treatment regimens (n = 187) with a cohort of matched patients with CP-B receiving BSC (n = 156). The first-line immunotherapies were the monotherapy nivolumab or the combination (atezolizumab plus bevacizumab).

Immunotherapy was linked with significantly lower risk of death, compared with best supportive care.

ICI exposure was associated with a reduction of about 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001).
 

Is immunotherapy or best supportive care the superior treatment?

The authors wrote that the results point to “improved survival in association with ICI treatment, compared with BSC in patients with uHCC with CP-B liver dysfunction.”

According to the study’s senior author David Pinato, MD, PhD, “this is the first study to suggest that there might be an advantage [of treatment with immunotherapy] in a proportion of people with Child-Pugh B liver dysfunction and particularly so in those patients with more limited disease and portal vein tumor thrombosis.”
 

Will the findings of this study make treatment allocation for patients with uHCC and moderate liver dysfunction (CP-B) less controversial?

Because it is a retrospective study, Dr. Pinato said in an interview, that the findings are not definitive, but can be used to inform future randomized controlled trials.

Dr. Pinato, who is also with the Imperial College London, added that the findings may also introduce a new question.

Although the study was not powered to look at survival differences across the two immunotherapy options given to the patients, there did not seem to be a striking difference between using one immunotherapy (nivolumab) or a combination (atezolizumab plus bevacizumab), he said.

“This is quite important because we know that combinations are significantly superior to monotherapy in patients with normal liver function but based on our study we might say that this provides preliminary evidence that [superiority of combination therapy] might not be true if the liver function is worse.”
 

What do these findings add to the literature about how best to treat patients with uHCC and suboptimal liver function?

Without evidence of efficacy and safety for the group in previous studies, the widespread recommendation for those with moderate dysfunction has been BSC.

These findings “pave the way to select potential patient subgroups in clinical practice,” Dr. Pinato said. It also suggests that the safety level of immunotherapy treatments is acceptable in this patient population, so they are not necessarily disadvantaged compared to patients with more preserved liver function.

“This is the best level of evidence currently available to guide treatment decisions in patients with Child-Pugh B who have been universally excluded by prospective clinical trials and for whom there is no randomized comparison,” Dr. Pinato said.

Dr. Pinato reported personal fees from Roche, AstraZeneca, Eisai, Mina Therapeutics, Starpharma, Lift Biosciences, Boston Scientific, and Avammune, and grants from GSK, MSD, and BMS outside the submitted work. Dr. Fulgenzi has no disclosures. Other authors of the new research have multiple ties with pharmaceutical companies. Complete disclosures are available with the full text of the journal article.

In the last 10 years, clinical outcomes have improved for patients with unresectable hepatocellular carcinoma (uHCC). The cancer generally comes with chronic liver inflammation, and liver cirrhosis is present in up to 80% of cases. The level of liver dysfunction helps determine the prognosis, but it also may affect the safety of delivering anticancer treatment.

Clinical trials that have tested systemic immunotherapies have excluded patients who don’t fall into the Child-Pugh class A criteria (CP-A) for liver disease, which is the least severe of the Child-Pugh classes A-C. Therefore, there has been much debate about whether patients who have more liver disease (moderate liver dysfunction) and fit under CP-B criteria, instead of CP-A, should be treated with immune checkpoint inhibitor (ICI) therapy or best supportive care (BSC).

A new study, led by Claudia Angela Maria Fulgenzi, MD, with the Department of Surgery and Cancer at the Imperial College London, England, published in JAMA Oncology on July 18, uses an alternative way to compare outcomes following two different paths of care for uHCC patients with moderate liver dysfunction.
 

How was the study done and what did the investigators find?

Researchers performed a retrospective, multicenter, international clinical case series of patients treated in routine practice in tertiary care centers across Europe, the United States, and Asia. They compared data from uHCC patients with CP-B who were receiving first-line ICI-based treatment regimens (n = 187) with a cohort of matched patients with CP-B receiving BSC (n = 156). The first-line immunotherapies were the monotherapy nivolumab or the combination (atezolizumab plus bevacizumab).

Immunotherapy was linked with significantly lower risk of death, compared with best supportive care.

ICI exposure was associated with a reduction of about 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001).
 

Is immunotherapy or best supportive care the superior treatment?

The authors wrote that the results point to “improved survival in association with ICI treatment, compared with BSC in patients with uHCC with CP-B liver dysfunction.”

According to the study’s senior author David Pinato, MD, PhD, “this is the first study to suggest that there might be an advantage [of treatment with immunotherapy] in a proportion of people with Child-Pugh B liver dysfunction and particularly so in those patients with more limited disease and portal vein tumor thrombosis.”
 

Will the findings of this study make treatment allocation for patients with uHCC and moderate liver dysfunction (CP-B) less controversial?

Because it is a retrospective study, Dr. Pinato said in an interview, that the findings are not definitive, but can be used to inform future randomized controlled trials.

Dr. Pinato, who is also with the Imperial College London, added that the findings may also introduce a new question.

Although the study was not powered to look at survival differences across the two immunotherapy options given to the patients, there did not seem to be a striking difference between using one immunotherapy (nivolumab) or a combination (atezolizumab plus bevacizumab), he said.

“This is quite important because we know that combinations are significantly superior to monotherapy in patients with normal liver function but based on our study we might say that this provides preliminary evidence that [superiority of combination therapy] might not be true if the liver function is worse.”
 

What do these findings add to the literature about how best to treat patients with uHCC and suboptimal liver function?

Without evidence of efficacy and safety for the group in previous studies, the widespread recommendation for those with moderate dysfunction has been BSC.

These findings “pave the way to select potential patient subgroups in clinical practice,” Dr. Pinato said. It also suggests that the safety level of immunotherapy treatments is acceptable in this patient population, so they are not necessarily disadvantaged compared to patients with more preserved liver function.

“This is the best level of evidence currently available to guide treatment decisions in patients with Child-Pugh B who have been universally excluded by prospective clinical trials and for whom there is no randomized comparison,” Dr. Pinato said.

Dr. Pinato reported personal fees from Roche, AstraZeneca, Eisai, Mina Therapeutics, Starpharma, Lift Biosciences, Boston Scientific, and Avammune, and grants from GSK, MSD, and BMS outside the submitted work. Dr. Fulgenzi has no disclosures. Other authors of the new research have multiple ties with pharmaceutical companies. Complete disclosures are available with the full text of the journal article.

In the last 10 years, clinical outcomes have improved for patients with unresectable hepatocellular carcinoma (uHCC). The cancer generally comes with chronic liver inflammation, and liver cirrhosis is present in up to 80% of cases. The level of liver dysfunction helps determine the prognosis, but it also may affect the safety of delivering anticancer treatment.

Clinical trials that have tested systemic immunotherapies have excluded patients who don’t fall into the Child-Pugh class A criteria (CP-A) for liver disease, which is the least severe of the Child-Pugh classes A-C. Therefore, there has been much debate about whether patients who have more liver disease (moderate liver dysfunction) and fit under CP-B criteria, instead of CP-A, should be treated with immune checkpoint inhibitor (ICI) therapy or best supportive care (BSC).

A new study, led by Claudia Angela Maria Fulgenzi, MD, with the Department of Surgery and Cancer at the Imperial College London, England, published in JAMA Oncology on July 18, uses an alternative way to compare outcomes following two different paths of care for uHCC patients with moderate liver dysfunction.
 

How was the study done and what did the investigators find?

Researchers performed a retrospective, multicenter, international clinical case series of patients treated in routine practice in tertiary care centers across Europe, the United States, and Asia. They compared data from uHCC patients with CP-B who were receiving first-line ICI-based treatment regimens (n = 187) with a cohort of matched patients with CP-B receiving BSC (n = 156). The first-line immunotherapies were the monotherapy nivolumab or the combination (atezolizumab plus bevacizumab).

Immunotherapy was linked with significantly lower risk of death, compared with best supportive care.

ICI exposure was associated with a reduction of about 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001).
 

Is immunotherapy or best supportive care the superior treatment?

The authors wrote that the results point to “improved survival in association with ICI treatment, compared with BSC in patients with uHCC with CP-B liver dysfunction.”

According to the study’s senior author David Pinato, MD, PhD, “this is the first study to suggest that there might be an advantage [of treatment with immunotherapy] in a proportion of people with Child-Pugh B liver dysfunction and particularly so in those patients with more limited disease and portal vein tumor thrombosis.”
 

Will the findings of this study make treatment allocation for patients with uHCC and moderate liver dysfunction (CP-B) less controversial?

Because it is a retrospective study, Dr. Pinato said in an interview, that the findings are not definitive, but can be used to inform future randomized controlled trials.

Dr. Pinato, who is also with the Imperial College London, added that the findings may also introduce a new question.

Although the study was not powered to look at survival differences across the two immunotherapy options given to the patients, there did not seem to be a striking difference between using one immunotherapy (nivolumab) or a combination (atezolizumab plus bevacizumab), he said.

“This is quite important because we know that combinations are significantly superior to monotherapy in patients with normal liver function but based on our study we might say that this provides preliminary evidence that [superiority of combination therapy] might not be true if the liver function is worse.”
 

What do these findings add to the literature about how best to treat patients with uHCC and suboptimal liver function?

Without evidence of efficacy and safety for the group in previous studies, the widespread recommendation for those with moderate dysfunction has been BSC.

These findings “pave the way to select potential patient subgroups in clinical practice,” Dr. Pinato said. It also suggests that the safety level of immunotherapy treatments is acceptable in this patient population, so they are not necessarily disadvantaged compared to patients with more preserved liver function.

“This is the best level of evidence currently available to guide treatment decisions in patients with Child-Pugh B who have been universally excluded by prospective clinical trials and for whom there is no randomized comparison,” Dr. Pinato said.

Dr. Pinato reported personal fees from Roche, AstraZeneca, Eisai, Mina Therapeutics, Starpharma, Lift Biosciences, Boston Scientific, and Avammune, and grants from GSK, MSD, and BMS outside the submitted work. Dr. Fulgenzi has no disclosures. Other authors of the new research have multiple ties with pharmaceutical companies. Complete disclosures are available with the full text of the journal article.

In the war against cancer, doctors and patients have long reached for three main weapons to target diseased cells: chemotherapy, radiation, and surgery.

But new research published this month in the journal Nature Materials suggests that manipulating the tissue around those cells — a strategy known as “mechanotherapeutics” — could play a critical role in reducing drug resistance and improving survival rates for hard-to-treat cancers like pancreatic cancer.

“Our study shows the importance of the tumor microenvironment and its properties in dictating how cancer progresses and responds to drug treatment,” said first author Bauer LeSavage, PhD, who conducted the study as a postdoctoral researcher in the Bioengineering Department at Stanford University, Stanford, California. “It also demonstrates that chemoresistance can be reversed.”

Each year, about 66,000 people are diagnosed with pancreatic cancer, and 52,000 die from it. It is a particularly lethal type of cancer, with 5-year survival rates hovering around 7% — a rate that has not improved much since 1996 when the first-line chemotherapy drug gemcitabine was approved.

It looks different from many cancers, said Lynn Matrisian, PhD, chief science officer for the nonprofit Pancreatic Cancer Action Network. Instead of a tumorous mass, it is made of islands of cancer cells surrounded by unusually dense fibrous tissue known as the extracellular matrix, which can collapse blood vessels and prevent drugs from reaching the tumor.

For the study, Dr. LeSavage and his team engineered synthetic but lifelike three-dimensional pancreas tissue with varying degrees of stiffness and different biochemical properties. Then they inserted bits of real tumors from patients with pancreatic cancer, watched them grow, and tried to kill them with drugs.

They found that cells growing in a stiff matrix were more resistant to chemotherapy than those growing in a softer matrix. But the story didn’t end there.

They also found that high amounts of the tissue-strengthening protein hyaluronic acid in stiff tissue seemed to signal the cancer cells to develop tiny pumps on their surface which shuttled out the drugs before they could take effect.

When the researchers moved the cancer cells into either a softer matrix or a stiff matrix in which the hyaluronic acid receptor, called CD44, was blocked, the chemotherapy drugs started working again.

“This suggests that if we can disrupt the stiffness signaling that’s happening through the CD44 receptor, we could make patients’ pancreatic cancer treatable again by normal chemotherapy,” said senior study author Sarah Heilshorn, PhD, a professor of materials science and engineering at Stanford. “These results suggest an exciting new direction for new drug development.”
 

Targeting Nearby Tissue: A Novel Approach to Fighting Chemoresistance

The study is not the first to suggest that chemically targeting the microenvironment surrounding a tumor can influence how patients respond to treatment.

In one recent clinical trial, patients with metastatic pancreatic cancer were given an experimental drug to inhibit a protein called connective tissue growth factor, reduce fibrous tissue, and make pancreatic tumors easier to surgically remove. Results have not been published yet.

Other research suggests that the generic blood pressure drug losartan, when given in combination with chemotherapy and radiation, can boost survival in patients with advanced pancreatic cancer by, in part, improving the health of blood vessels that carry drugs to the tumor.

But other studies of such mechanotherapeutics have yielded inconclusive results, said Dr. Matrisian.

“This paper points to another reason why we should not give up on this approach,” she said.

Ning Wang, PhD, director of the new Institute for Mechanobiology at Northeastern University College of Engineering, Boston, said there is no question that the composition of a tumor’s environment can influence how cancer progresses or responds to drugs. The new paper, he said, adds an important new chapter to the evolving story.

“But it’s very complicated. It’s not as simple as saying make it softer or stiffer and you can change the outcome for the patient,” Dr. Wang said.

In fact, some research has shown that tissue becomes stiffer when cancer arises so it can contain it from spreading.

In one animal study of pancreatic cancer that had spread to the liver, administering drugs to soften the surrounding tissue, or stroma, actually had the opposite effect — accelerating tumor growth and reducing survival rates.

Dr. Wang also noted that any drug designed to influence the extracellular matrix would need to be extremely localized, to prevent damage to other tissues, like bone or heart muscle.

Dr. LeSavage said he sees the paper as a case study in how important the extracellular matrix is and an example of how artificially grown organs or tissues can play a key role in testing how drugs work or don’t work.

He imagines a day when doctors could personalize treatments by taking a bit of a patient’s tumor, growing it in artificial tissue, and seeing how different tissue-altering drugs affect different therapies.

“This isn’t something that is just unique to pancreatic cancer,” he said, noting that the extracellular matrix throughout the body interacts with different cancers. “If we could take someone who has a chemoresistant tumor and convert it into something that is sensitive to existing therapies again, we could give them a second chance.”

A version of this article appeared on Medscape.com.

In the war against cancer, doctors and patients have long reached for three main weapons to target diseased cells: chemotherapy, radiation, and surgery.

But new research published this month in the journal Nature Materials suggests that manipulating the tissue around those cells — a strategy known as “mechanotherapeutics” — could play a critical role in reducing drug resistance and improving survival rates for hard-to-treat cancers like pancreatic cancer.

“Our study shows the importance of the tumor microenvironment and its properties in dictating how cancer progresses and responds to drug treatment,” said first author Bauer LeSavage, PhD, who conducted the study as a postdoctoral researcher in the Bioengineering Department at Stanford University, Stanford, California. “It also demonstrates that chemoresistance can be reversed.”

Each year, about 66,000 people are diagnosed with pancreatic cancer, and 52,000 die from it. It is a particularly lethal type of cancer, with 5-year survival rates hovering around 7% — a rate that has not improved much since 1996 when the first-line chemotherapy drug gemcitabine was approved.

It looks different from many cancers, said Lynn Matrisian, PhD, chief science officer for the nonprofit Pancreatic Cancer Action Network. Instead of a tumorous mass, it is made of islands of cancer cells surrounded by unusually dense fibrous tissue known as the extracellular matrix, which can collapse blood vessels and prevent drugs from reaching the tumor.

For the study, Dr. LeSavage and his team engineered synthetic but lifelike three-dimensional pancreas tissue with varying degrees of stiffness and different biochemical properties. Then they inserted bits of real tumors from patients with pancreatic cancer, watched them grow, and tried to kill them with drugs.

They found that cells growing in a stiff matrix were more resistant to chemotherapy than those growing in a softer matrix. But the story didn’t end there.

They also found that high amounts of the tissue-strengthening protein hyaluronic acid in stiff tissue seemed to signal the cancer cells to develop tiny pumps on their surface which shuttled out the drugs before they could take effect.

When the researchers moved the cancer cells into either a softer matrix or a stiff matrix in which the hyaluronic acid receptor, called CD44, was blocked, the chemotherapy drugs started working again.

“This suggests that if we can disrupt the stiffness signaling that’s happening through the CD44 receptor, we could make patients’ pancreatic cancer treatable again by normal chemotherapy,” said senior study author Sarah Heilshorn, PhD, a professor of materials science and engineering at Stanford. “These results suggest an exciting new direction for new drug development.”
 

Targeting Nearby Tissue: A Novel Approach to Fighting Chemoresistance

The study is not the first to suggest that chemically targeting the microenvironment surrounding a tumor can influence how patients respond to treatment.

In one recent clinical trial, patients with metastatic pancreatic cancer were given an experimental drug to inhibit a protein called connective tissue growth factor, reduce fibrous tissue, and make pancreatic tumors easier to surgically remove. Results have not been published yet.

Other research suggests that the generic blood pressure drug losartan, when given in combination with chemotherapy and radiation, can boost survival in patients with advanced pancreatic cancer by, in part, improving the health of blood vessels that carry drugs to the tumor.

But other studies of such mechanotherapeutics have yielded inconclusive results, said Dr. Matrisian.

“This paper points to another reason why we should not give up on this approach,” she said.

Ning Wang, PhD, director of the new Institute for Mechanobiology at Northeastern University College of Engineering, Boston, said there is no question that the composition of a tumor’s environment can influence how cancer progresses or responds to drugs. The new paper, he said, adds an important new chapter to the evolving story.

“But it’s very complicated. It’s not as simple as saying make it softer or stiffer and you can change the outcome for the patient,” Dr. Wang said.

In fact, some research has shown that tissue becomes stiffer when cancer arises so it can contain it from spreading.

In one animal study of pancreatic cancer that had spread to the liver, administering drugs to soften the surrounding tissue, or stroma, actually had the opposite effect — accelerating tumor growth and reducing survival rates.

Dr. Wang also noted that any drug designed to influence the extracellular matrix would need to be extremely localized, to prevent damage to other tissues, like bone or heart muscle.

Dr. LeSavage said he sees the paper as a case study in how important the extracellular matrix is and an example of how artificially grown organs or tissues can play a key role in testing how drugs work or don’t work.

He imagines a day when doctors could personalize treatments by taking a bit of a patient’s tumor, growing it in artificial tissue, and seeing how different tissue-altering drugs affect different therapies.

“This isn’t something that is just unique to pancreatic cancer,” he said, noting that the extracellular matrix throughout the body interacts with different cancers. “If we could take someone who has a chemoresistant tumor and convert it into something that is sensitive to existing therapies again, we could give them a second chance.”

A version of this article appeared on Medscape.com.

In the war against cancer, doctors and patients have long reached for three main weapons to target diseased cells: chemotherapy, radiation, and surgery.

But new research published this month in the journal Nature Materials suggests that manipulating the tissue around those cells — a strategy known as “mechanotherapeutics” — could play a critical role in reducing drug resistance and improving survival rates for hard-to-treat cancers like pancreatic cancer.

“Our study shows the importance of the tumor microenvironment and its properties in dictating how cancer progresses and responds to drug treatment,” said first author Bauer LeSavage, PhD, who conducted the study as a postdoctoral researcher in the Bioengineering Department at Stanford University, Stanford, California. “It also demonstrates that chemoresistance can be reversed.”

Each year, about 66,000 people are diagnosed with pancreatic cancer, and 52,000 die from it. It is a particularly lethal type of cancer, with 5-year survival rates hovering around 7% — a rate that has not improved much since 1996 when the first-line chemotherapy drug gemcitabine was approved.

It looks different from many cancers, said Lynn Matrisian, PhD, chief science officer for the nonprofit Pancreatic Cancer Action Network. Instead of a tumorous mass, it is made of islands of cancer cells surrounded by unusually dense fibrous tissue known as the extracellular matrix, which can collapse blood vessels and prevent drugs from reaching the tumor.

For the study, Dr. LeSavage and his team engineered synthetic but lifelike three-dimensional pancreas tissue with varying degrees of stiffness and different biochemical properties. Then they inserted bits of real tumors from patients with pancreatic cancer, watched them grow, and tried to kill them with drugs.

They found that cells growing in a stiff matrix were more resistant to chemotherapy than those growing in a softer matrix. But the story didn’t end there.

They also found that high amounts of the tissue-strengthening protein hyaluronic acid in stiff tissue seemed to signal the cancer cells to develop tiny pumps on their surface which shuttled out the drugs before they could take effect.

When the researchers moved the cancer cells into either a softer matrix or a stiff matrix in which the hyaluronic acid receptor, called CD44, was blocked, the chemotherapy drugs started working again.

“This suggests that if we can disrupt the stiffness signaling that’s happening through the CD44 receptor, we could make patients’ pancreatic cancer treatable again by normal chemotherapy,” said senior study author Sarah Heilshorn, PhD, a professor of materials science and engineering at Stanford. “These results suggest an exciting new direction for new drug development.”
 

Targeting Nearby Tissue: A Novel Approach to Fighting Chemoresistance

The study is not the first to suggest that chemically targeting the microenvironment surrounding a tumor can influence how patients respond to treatment.

In one recent clinical trial, patients with metastatic pancreatic cancer were given an experimental drug to inhibit a protein called connective tissue growth factor, reduce fibrous tissue, and make pancreatic tumors easier to surgically remove. Results have not been published yet.

Other research suggests that the generic blood pressure drug losartan, when given in combination with chemotherapy and radiation, can boost survival in patients with advanced pancreatic cancer by, in part, improving the health of blood vessels that carry drugs to the tumor.

But other studies of such mechanotherapeutics have yielded inconclusive results, said Dr. Matrisian.

“This paper points to another reason why we should not give up on this approach,” she said.

Ning Wang, PhD, director of the new Institute for Mechanobiology at Northeastern University College of Engineering, Boston, said there is no question that the composition of a tumor’s environment can influence how cancer progresses or responds to drugs. The new paper, he said, adds an important new chapter to the evolving story.

“But it’s very complicated. It’s not as simple as saying make it softer or stiffer and you can change the outcome for the patient,” Dr. Wang said.

In fact, some research has shown that tissue becomes stiffer when cancer arises so it can contain it from spreading.

In one animal study of pancreatic cancer that had spread to the liver, administering drugs to soften the surrounding tissue, or stroma, actually had the opposite effect — accelerating tumor growth and reducing survival rates.

Dr. Wang also noted that any drug designed to influence the extracellular matrix would need to be extremely localized, to prevent damage to other tissues, like bone or heart muscle.

Dr. LeSavage said he sees the paper as a case study in how important the extracellular matrix is and an example of how artificially grown organs or tissues can play a key role in testing how drugs work or don’t work.

He imagines a day when doctors could personalize treatments by taking a bit of a patient’s tumor, growing it in artificial tissue, and seeing how different tissue-altering drugs affect different therapies.

“This isn’t something that is just unique to pancreatic cancer,” he said, noting that the extracellular matrix throughout the body interacts with different cancers. “If we could take someone who has a chemoresistant tumor and convert it into something that is sensitive to existing therapies again, we could give them a second chance.”

A version of this article appeared on Medscape.com.

TOPLINE:

Surveillance of high-risk individuals may detect pancreatic ductal adenocarcinoma at an earlier stage, when the tumor is smaller and easier to treat, and could help improve survival in this population.

METHODOLOGY:

• Pancreatic ductal adenocarcinoma has poor 5-year survival rates and is often detected at later stages. General population screening is not recommended, but high-risk individuals, such as those with familial or genetic predispositions, may benefit from regular surveillance.
• The Cancer of the Pancreas Screening (CAPS) program, initiated in 1998, has been evaluating the effectiveness of such targeted surveillance for over two decades, but whether targeted surveillance confers a survival benefit remains unclear.
• The current study evaluated 26 high-risk individuals in the CAPS program who were ultimately diagnosed with pancreatic ductal adenocarcinoma. These high-risk individuals had undergone surveillance with annual endoscopic ultrasonography or MRI prior to diagnosis.
• The researchers compared these 26 individuals with 1504 matched control patients with pancreatic ductal adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database. The high-risk individuals and SEER control patients were matched on age, sex, and year of diagnosis.
• The primary outcomes were tumor stage at diagnosis, overall survival, and pancreatic cancer-specific mortality.

TAKEAWAY:

• High-risk individuals were significantly more likely to be diagnosed with early-stage pancreatic cancer: 38.5% were diagnosed at stage I vs 10.3% in the general US population, and 30.8% were diagnosed at stage II vs 25.1% in the general US population (P < .001).
• The median tumor size at diagnosis was smaller in high-risk individuals than in control patients (2.5 vs 3.6 cm; P < .001), and significantly fewer high-risk individuals had distant metastases at diagnosis (M1 stage) vs control patients (26.9% vs 53.8%; P = .01).
• Overall, high-risk individuals lived about 4.5 years longer — median of 61.7 months vs 8 months for control patients (hazard ratio [HR], 4.19; P < .001). In the 20 high-risk patients with screen-detected cancer, median overall survival was even higher at 144 months.
• The probability of surviving 5 years was significantly better in the high-risk group (50%) than in the control group (9%). And at 5 years, high-risk individuals had a significantly lower probability of dying from pancreatic cancer (HR, 3.58; P < .001).

IN PRACTICE:

Surveillance of high-risk individuals led to detection of “smaller pancreatic cancers, a greater number of patients with stage I disease,” as well as “a much higher likelihood of long-term survival than unscreened patients in the general population,” the authors concluded. “These findings suggest that selective surveillance of individuals at high risk for pancreatic cancer may improve clinical outcomes.”

SOURCE:

This study, with first author Amanda L. Blackford, from Johns Hopkins Medical Institutions, Baltimore, was published online July 3 in JAMA Oncology.

LIMITATIONS:

The findings might have limited generalizability due to enrollment at academic referral centers, limited racial and ethnic diversity, and a small number of high-risk individuals progressing to pancreatic cancer. The study also lacked a control group of unscreened high-risk individuals.

DISCLOSURES:

This study was supported by the National Institutes of Health, Susan Wojcicki and Dennis Troper, and others. Several authors reported financial ties outside this work.

A version of this article appeared on Medscape.com.

TOPLINE:

Surveillance of high-risk individuals may detect pancreatic ductal adenocarcinoma at an earlier stage, when the tumor is smaller and easier to treat, and could help improve survival in this population.

METHODOLOGY:

• Pancreatic ductal adenocarcinoma has poor 5-year survival rates and is often detected at later stages. General population screening is not recommended, but high-risk individuals, such as those with familial or genetic predispositions, may benefit from regular surveillance.
• The Cancer of the Pancreas Screening (CAPS) program, initiated in 1998, has been evaluating the effectiveness of such targeted surveillance for over two decades, but whether targeted surveillance confers a survival benefit remains unclear.
• The current study evaluated 26 high-risk individuals in the CAPS program who were ultimately diagnosed with pancreatic ductal adenocarcinoma. These high-risk individuals had undergone surveillance with annual endoscopic ultrasonography or MRI prior to diagnosis.
• The researchers compared these 26 individuals with 1504 matched control patients with pancreatic ductal adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database. The high-risk individuals and SEER control patients were matched on age, sex, and year of diagnosis.
• The primary outcomes were tumor stage at diagnosis, overall survival, and pancreatic cancer-specific mortality.

TAKEAWAY:

• High-risk individuals were significantly more likely to be diagnosed with early-stage pancreatic cancer: 38.5% were diagnosed at stage I vs 10.3% in the general US population, and 30.8% were diagnosed at stage II vs 25.1% in the general US population (P < .001).
• The median tumor size at diagnosis was smaller in high-risk individuals than in control patients (2.5 vs 3.6 cm; P < .001), and significantly fewer high-risk individuals had distant metastases at diagnosis (M1 stage) vs control patients (26.9% vs 53.8%; P = .01).
• Overall, high-risk individuals lived about 4.5 years longer — median of 61.7 months vs 8 months for control patients (hazard ratio [HR], 4.19; P < .001). In the 20 high-risk patients with screen-detected cancer, median overall survival was even higher at 144 months.
• The probability of surviving 5 years was significantly better in the high-risk group (50%) than in the control group (9%). And at 5 years, high-risk individuals had a significantly lower probability of dying from pancreatic cancer (HR, 3.58; P < .001).

IN PRACTICE:

Surveillance of high-risk individuals led to detection of “smaller pancreatic cancers, a greater number of patients with stage I disease,” as well as “a much higher likelihood of long-term survival than unscreened patients in the general population,” the authors concluded. “These findings suggest that selective surveillance of individuals at high risk for pancreatic cancer may improve clinical outcomes.”

SOURCE:

This study, with first author Amanda L. Blackford, from Johns Hopkins Medical Institutions, Baltimore, was published online July 3 in JAMA Oncology.

LIMITATIONS:

The findings might have limited generalizability due to enrollment at academic referral centers, limited racial and ethnic diversity, and a small number of high-risk individuals progressing to pancreatic cancer. The study also lacked a control group of unscreened high-risk individuals.

DISCLOSURES:

This study was supported by the National Institutes of Health, Susan Wojcicki and Dennis Troper, and others. Several authors reported financial ties outside this work.

A version of this article appeared on Medscape.com.

TOPLINE:

Surveillance of high-risk individuals may detect pancreatic ductal adenocarcinoma at an earlier stage, when the tumor is smaller and easier to treat, and could help improve survival in this population.

METHODOLOGY:

• Pancreatic ductal adenocarcinoma has poor 5-year survival rates and is often detected at later stages. General population screening is not recommended, but high-risk individuals, such as those with familial or genetic predispositions, may benefit from regular surveillance.
• The Cancer of the Pancreas Screening (CAPS) program, initiated in 1998, has been evaluating the effectiveness of such targeted surveillance for over two decades, but whether targeted surveillance confers a survival benefit remains unclear.
• The current study evaluated 26 high-risk individuals in the CAPS program who were ultimately diagnosed with pancreatic ductal adenocarcinoma. These high-risk individuals had undergone surveillance with annual endoscopic ultrasonography or MRI prior to diagnosis.
• The researchers compared these 26 individuals with 1504 matched control patients with pancreatic ductal adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database. The high-risk individuals and SEER control patients were matched on age, sex, and year of diagnosis.
• The primary outcomes were tumor stage at diagnosis, overall survival, and pancreatic cancer-specific mortality.

TAKEAWAY:

• High-risk individuals were significantly more likely to be diagnosed with early-stage pancreatic cancer: 38.5% were diagnosed at stage I vs 10.3% in the general US population, and 30.8% were diagnosed at stage II vs 25.1% in the general US population (P < .001).
• The median tumor size at diagnosis was smaller in high-risk individuals than in control patients (2.5 vs 3.6 cm; P < .001), and significantly fewer high-risk individuals had distant metastases at diagnosis (M1 stage) vs control patients (26.9% vs 53.8%; P = .01).
• Overall, high-risk individuals lived about 4.5 years longer — median of 61.7 months vs 8 months for control patients (hazard ratio [HR], 4.19; P < .001). In the 20 high-risk patients with screen-detected cancer, median overall survival was even higher at 144 months.
• The probability of surviving 5 years was significantly better in the high-risk group (50%) than in the control group (9%). And at 5 years, high-risk individuals had a significantly lower probability of dying from pancreatic cancer (HR, 3.58; P < .001).

IN PRACTICE:

Surveillance of high-risk individuals led to detection of “smaller pancreatic cancers, a greater number of patients with stage I disease,” as well as “a much higher likelihood of long-term survival than unscreened patients in the general population,” the authors concluded. “These findings suggest that selective surveillance of individuals at high risk for pancreatic cancer may improve clinical outcomes.”

SOURCE:

This study, with first author Amanda L. Blackford, from Johns Hopkins Medical Institutions, Baltimore, was published online July 3 in JAMA Oncology.

LIMITATIONS:

The findings might have limited generalizability due to enrollment at academic referral centers, limited racial and ethnic diversity, and a small number of high-risk individuals progressing to pancreatic cancer. The study also lacked a control group of unscreened high-risk individuals.

DISCLOSURES:

This study was supported by the National Institutes of Health, Susan Wojcicki and Dennis Troper, and others. Several authors reported financial ties outside this work.

A version of this article appeared on Medscape.com.

TOPLINE:

For patients with gastric cancer, extending regular follow-up beyond the typical 5 years after gastrectomy was associated with improved overall and post-recurrence survival rates, new data from a retrospective analysis showed.

METHODOLOGY:

• Currently, postgastrectomy cancer surveillance typically lasts 5 years, although some centers now monitor patients beyond this point.
• To investigate the potential benefit of extended surveillance, researchers used Korean National Health Insurance claims data to identify 40,468 patients with gastric cancer who were disease free 5 years after gastrectomy — 14,294 received extended regular follow-up visits and 26,174 did not.
• The extended regular follow-up group was defined as having endoscopy or abdominopelvic CT between 2 months and 2 years before diagnosis of late recurrence or gastric remnant cancer and having two or more examinations between 5.5 and 8.5 years after gastrectomy. Late recurrence was a recurrence diagnosed 5 years after gastrectomy.
• Researchers used Cox proportional hazards regression to evaluate the independent association between follow-up and overall and postrecurrence survival rates.

TAKEAWAY:

• Overall, 5 years postgastrectomy, the incidence of late recurrence or gastric remnant cancer was 7.8% — 4.0% between 5 and 10 years (1610 of 40,468 patients) and 9.4% after 10 years (1528 of 16,287 patients).
• Regular follow-up beyond 5 years was associated with a significant reduction in overall mortality — from 49.4% to 36.9% at 15 years (P < .001). Overall survival after late recurrence or gastric remnant cancer also improved significantly with extended regular follow-up, with the 5-year postrecurrence survival rate increasing from 32.7% to 71.1% (P < .001).
• The combination of endoscopy and abdominopelvic CT provided the highest 5-year postrecurrence survival rate (74.5%), compared with endoscopy alone (54.5%) or CT alone (47.1%).
• A time interval of more than 2 years between a previous endoscopy or abdominopelvic CT and diagnosis of late recurrence or gastric remnant cancer significantly decreased postrecurrence survival (hazard ratio [HR], 1.72 for endoscopy and HR, 1.48 for abdominopelvic CT).

IN PRACTICE:

“These findings suggest that extended regular follow-up after 5 years post gastrectomy should be implemented clinically and that current practice and value of follow-up protocols in postoperative care of patients with gastric cancer be reconsidered,” the authors concluded.

The authors of an accompanying commentary cautioned that, while the study “successfully establishes groundwork for extending surveillance of gastric cancer in high-risk populations, more work is needed to strategically identify those who would benefit most from extended surveillance.”
 

SOURCE:

The study, with first author Ju-Hee Lee, MD, PhD, Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea, and accompanying commentary were published online on June 18 in JAMA Surgery.

LIMITATIONS:

Recurrent cancer and gastric remnant cancer could not be distinguished from each other because clinical records were not analyzed. The claims database lacked detailed clinical information on individual patients, including cancer stages, and a separate analysis of tumor markers could not be performed.

DISCLOSURES:

The study was funded by a grant from the Korean Gastric Cancer Association. The study authors and commentary authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

For patients with gastric cancer, extending regular follow-up beyond the typical 5 years after gastrectomy was associated with improved overall and post-recurrence survival rates, new data from a retrospective analysis showed.

METHODOLOGY:

• Currently, postgastrectomy cancer surveillance typically lasts 5 years, although some centers now monitor patients beyond this point.
• To investigate the potential benefit of extended surveillance, researchers used Korean National Health Insurance claims data to identify 40,468 patients with gastric cancer who were disease free 5 years after gastrectomy — 14,294 received extended regular follow-up visits and 26,174 did not.
• The extended regular follow-up group was defined as having endoscopy or abdominopelvic CT between 2 months and 2 years before diagnosis of late recurrence or gastric remnant cancer and having two or more examinations between 5.5 and 8.5 years after gastrectomy. Late recurrence was a recurrence diagnosed 5 years after gastrectomy.
• Researchers used Cox proportional hazards regression to evaluate the independent association between follow-up and overall and postrecurrence survival rates.

TAKEAWAY:

• Overall, 5 years postgastrectomy, the incidence of late recurrence or gastric remnant cancer was 7.8% — 4.0% between 5 and 10 years (1610 of 40,468 patients) and 9.4% after 10 years (1528 of 16,287 patients).
• Regular follow-up beyond 5 years was associated with a significant reduction in overall mortality — from 49.4% to 36.9% at 15 years (P < .001). Overall survival after late recurrence or gastric remnant cancer also improved significantly with extended regular follow-up, with the 5-year postrecurrence survival rate increasing from 32.7% to 71.1% (P < .001).
• The combination of endoscopy and abdominopelvic CT provided the highest 5-year postrecurrence survival rate (74.5%), compared with endoscopy alone (54.5%) or CT alone (47.1%).
• A time interval of more than 2 years between a previous endoscopy or abdominopelvic CT and diagnosis of late recurrence or gastric remnant cancer significantly decreased postrecurrence survival (hazard ratio [HR], 1.72 for endoscopy and HR, 1.48 for abdominopelvic CT).

IN PRACTICE:

“These findings suggest that extended regular follow-up after 5 years post gastrectomy should be implemented clinically and that current practice and value of follow-up protocols in postoperative care of patients with gastric cancer be reconsidered,” the authors concluded.

The authors of an accompanying commentary cautioned that, while the study “successfully establishes groundwork for extending surveillance of gastric cancer in high-risk populations, more work is needed to strategically identify those who would benefit most from extended surveillance.”
 

SOURCE:

The study, with first author Ju-Hee Lee, MD, PhD, Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea, and accompanying commentary were published online on June 18 in JAMA Surgery.

LIMITATIONS:

Recurrent cancer and gastric remnant cancer could not be distinguished from each other because clinical records were not analyzed. The claims database lacked detailed clinical information on individual patients, including cancer stages, and a separate analysis of tumor markers could not be performed.

DISCLOSURES:

The study was funded by a grant from the Korean Gastric Cancer Association. The study authors and commentary authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

For patients with gastric cancer, extending regular follow-up beyond the typical 5 years after gastrectomy was associated with improved overall and post-recurrence survival rates, new data from a retrospective analysis showed.

METHODOLOGY:

• Currently, postgastrectomy cancer surveillance typically lasts 5 years, although some centers now monitor patients beyond this point.
• To investigate the potential benefit of extended surveillance, researchers used Korean National Health Insurance claims data to identify 40,468 patients with gastric cancer who were disease free 5 years after gastrectomy — 14,294 received extended regular follow-up visits and 26,174 did not.
• The extended regular follow-up group was defined as having endoscopy or abdominopelvic CT between 2 months and 2 years before diagnosis of late recurrence or gastric remnant cancer and having two or more examinations between 5.5 and 8.5 years after gastrectomy. Late recurrence was a recurrence diagnosed 5 years after gastrectomy.
• Researchers used Cox proportional hazards regression to evaluate the independent association between follow-up and overall and postrecurrence survival rates.

TAKEAWAY:

• Overall, 5 years postgastrectomy, the incidence of late recurrence or gastric remnant cancer was 7.8% — 4.0% between 5 and 10 years (1610 of 40,468 patients) and 9.4% after 10 years (1528 of 16,287 patients).
• Regular follow-up beyond 5 years was associated with a significant reduction in overall mortality — from 49.4% to 36.9% at 15 years (P < .001). Overall survival after late recurrence or gastric remnant cancer also improved significantly with extended regular follow-up, with the 5-year postrecurrence survival rate increasing from 32.7% to 71.1% (P < .001).
• The combination of endoscopy and abdominopelvic CT provided the highest 5-year postrecurrence survival rate (74.5%), compared with endoscopy alone (54.5%) or CT alone (47.1%).
• A time interval of more than 2 years between a previous endoscopy or abdominopelvic CT and diagnosis of late recurrence or gastric remnant cancer significantly decreased postrecurrence survival (hazard ratio [HR], 1.72 for endoscopy and HR, 1.48 for abdominopelvic CT).

IN PRACTICE:

“These findings suggest that extended regular follow-up after 5 years post gastrectomy should be implemented clinically and that current practice and value of follow-up protocols in postoperative care of patients with gastric cancer be reconsidered,” the authors concluded.

The authors of an accompanying commentary cautioned that, while the study “successfully establishes groundwork for extending surveillance of gastric cancer in high-risk populations, more work is needed to strategically identify those who would benefit most from extended surveillance.”
 

SOURCE:

The study, with first author Ju-Hee Lee, MD, PhD, Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea, and accompanying commentary were published online on June 18 in JAMA Surgery.

LIMITATIONS:

Recurrent cancer and gastric remnant cancer could not be distinguished from each other because clinical records were not analyzed. The claims database lacked detailed clinical information on individual patients, including cancer stages, and a separate analysis of tumor markers could not be performed.

DISCLOSURES:

The study was funded by a grant from the Korean Gastric Cancer Association. The study authors and commentary authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Achieving a pathologic complete response was associated with a twofold higher 5-year overall survival rate among patients with localized pancreatic adenocarcinoma who underwent preoperative chemo(radio)therapy and resection, a multicenter cohort study found. Several factors, including treatment type and tumor features, influenced the outcomes.

METHODOLOGY:

• Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma and may improve the chance of a pathologic complete response. Achieving a pathologic complete response is associated with improved overall survival.
• However, the evidence on pathologic complete response is based on large national databases or small single-center series. Multicenter studies with in-depth data about complete response are lacking.
• In the current analysis, researchers investigated the incidence and factors associated with pathologic complete response after preoperative chemo(radio)therapy among 1758 patients (mean age, 64 years; 50% men) with localized pancreatic adenocarcinoma who underwent resection after two or more cycles of chemotherapy (with or without radiotherapy).
• Patients were treated at 19 centers in eight countries. The median follow-up was 19 months. Pathologic complete response was defined as the absence of vital tumor cells in the patient’s sampled pancreas specimen after resection.
• Factors associated with overall survival and pathologic complete response were investigated with Cox proportional hazards and logistic regression models, respectively.

TAKEAWAY:

• Researchers found that the rate of pathologic complete response was 4.8% in patients who received chemo(radio)therapy before pancreatic cancer resection.
• Having a pathologic complete response was associated with a 54% lower risk for death (hazard ratio, 0.46). At 5 years, the overall survival rate was 63% in patients with a pathologic complete response vs 30% in patients without one.
• More patients who received preoperative modified FOLFIRINOX achieved a pathologic complete response (58.8% vs 44.7%). Other factors associated with pathologic complete response included tumors located in the pancreatic head (odds ratio [OR], 2.51), tumors > 40 mm at diagnosis (OR, 2.58), partial or complete radiologic response (OR, 13.0), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76).
• Preoperative radiotherapy (OR, 2.03) and preoperative stereotactic body radiotherapy (OR, 8.91) were also associated with a pathologic complete response; however, preoperative radiotherapy did not improve overall survival, and preoperative stereotactic body radiotherapy was independently associated with worse overall survival. These findings suggest that a pathologic complete response might not always reflect an optimal disease response.

IN PRACTICE:

Although pathologic complete response does not reflect cure, it is associated with better overall survival, the authors wrote. Factors associated with a pathologic complete response may inform treatment decisions.

SOURCE:

The study, with first author Thomas F. Stoop, MD, University of Amsterdam, the Netherlands, was published online on June 18 in JAMA Network Open.

LIMITATIONS:

The study had several limitations. The sample size and the limited number of events precluded comparative subanalyses, as well as a more detailed stratification for preoperative chemotherapy regimens. Information about patients’ race and the presence of BRCA germline mutations, both of which seem to be relevant to the chance of achieving a major pathologic response, was not collected or available.

DISCLOSURES:

No specific funding was noted. Several coauthors have industry relationships outside of the submitted work.

A version of this article first appeared on Medscape.com.

TOPLINE:

Achieving a pathologic complete response was associated with a twofold higher 5-year overall survival rate among patients with localized pancreatic adenocarcinoma who underwent preoperative chemo(radio)therapy and resection, a multicenter cohort study found. Several factors, including treatment type and tumor features, influenced the outcomes.

METHODOLOGY:

• Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma and may improve the chance of a pathologic complete response. Achieving a pathologic complete response is associated with improved overall survival.
• However, the evidence on pathologic complete response is based on large national databases or small single-center series. Multicenter studies with in-depth data about complete response are lacking.
• In the current analysis, researchers investigated the incidence and factors associated with pathologic complete response after preoperative chemo(radio)therapy among 1758 patients (mean age, 64 years; 50% men) with localized pancreatic adenocarcinoma who underwent resection after two or more cycles of chemotherapy (with or without radiotherapy).
• Patients were treated at 19 centers in eight countries. The median follow-up was 19 months. Pathologic complete response was defined as the absence of vital tumor cells in the patient’s sampled pancreas specimen after resection.
• Factors associated with overall survival and pathologic complete response were investigated with Cox proportional hazards and logistic regression models, respectively.

TAKEAWAY:

• Researchers found that the rate of pathologic complete response was 4.8% in patients who received chemo(radio)therapy before pancreatic cancer resection.
• Having a pathologic complete response was associated with a 54% lower risk for death (hazard ratio, 0.46). At 5 years, the overall survival rate was 63% in patients with a pathologic complete response vs 30% in patients without one.
• More patients who received preoperative modified FOLFIRINOX achieved a pathologic complete response (58.8% vs 44.7%). Other factors associated with pathologic complete response included tumors located in the pancreatic head (odds ratio [OR], 2.51), tumors > 40 mm at diagnosis (OR, 2.58), partial or complete radiologic response (OR, 13.0), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76).
• Preoperative radiotherapy (OR, 2.03) and preoperative stereotactic body radiotherapy (OR, 8.91) were also associated with a pathologic complete response; however, preoperative radiotherapy did not improve overall survival, and preoperative stereotactic body radiotherapy was independently associated with worse overall survival. These findings suggest that a pathologic complete response might not always reflect an optimal disease response.

IN PRACTICE:

Although pathologic complete response does not reflect cure, it is associated with better overall survival, the authors wrote. Factors associated with a pathologic complete response may inform treatment decisions.

SOURCE:

The study, with first author Thomas F. Stoop, MD, University of Amsterdam, the Netherlands, was published online on June 18 in JAMA Network Open.

LIMITATIONS:

The study had several limitations. The sample size and the limited number of events precluded comparative subanalyses, as well as a more detailed stratification for preoperative chemotherapy regimens. Information about patients’ race and the presence of BRCA germline mutations, both of which seem to be relevant to the chance of achieving a major pathologic response, was not collected or available.

DISCLOSURES:

No specific funding was noted. Several coauthors have industry relationships outside of the submitted work.

A version of this article first appeared on Medscape.com.

TOPLINE:

Achieving a pathologic complete response was associated with a twofold higher 5-year overall survival rate among patients with localized pancreatic adenocarcinoma who underwent preoperative chemo(radio)therapy and resection, a multicenter cohort study found. Several factors, including treatment type and tumor features, influenced the outcomes.

METHODOLOGY:

• Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma and may improve the chance of a pathologic complete response. Achieving a pathologic complete response is associated with improved overall survival.
• However, the evidence on pathologic complete response is based on large national databases or small single-center series. Multicenter studies with in-depth data about complete response are lacking.
• In the current analysis, researchers investigated the incidence and factors associated with pathologic complete response after preoperative chemo(radio)therapy among 1758 patients (mean age, 64 years; 50% men) with localized pancreatic adenocarcinoma who underwent resection after two or more cycles of chemotherapy (with or without radiotherapy).
• Patients were treated at 19 centers in eight countries. The median follow-up was 19 months. Pathologic complete response was defined as the absence of vital tumor cells in the patient’s sampled pancreas specimen after resection.
• Factors associated with overall survival and pathologic complete response were investigated with Cox proportional hazards and logistic regression models, respectively.

TAKEAWAY:

• Researchers found that the rate of pathologic complete response was 4.8% in patients who received chemo(radio)therapy before pancreatic cancer resection.
• Having a pathologic complete response was associated with a 54% lower risk for death (hazard ratio, 0.46). At 5 years, the overall survival rate was 63% in patients with a pathologic complete response vs 30% in patients without one.
• More patients who received preoperative modified FOLFIRINOX achieved a pathologic complete response (58.8% vs 44.7%). Other factors associated with pathologic complete response included tumors located in the pancreatic head (odds ratio [OR], 2.51), tumors > 40 mm at diagnosis (OR, 2.58), partial or complete radiologic response (OR, 13.0), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76).
• Preoperative radiotherapy (OR, 2.03) and preoperative stereotactic body radiotherapy (OR, 8.91) were also associated with a pathologic complete response; however, preoperative radiotherapy did not improve overall survival, and preoperative stereotactic body radiotherapy was independently associated with worse overall survival. These findings suggest that a pathologic complete response might not always reflect an optimal disease response.

IN PRACTICE:

Although pathologic complete response does not reflect cure, it is associated with better overall survival, the authors wrote. Factors associated with a pathologic complete response may inform treatment decisions.

SOURCE:

The study, with first author Thomas F. Stoop, MD, University of Amsterdam, the Netherlands, was published online on June 18 in JAMA Network Open.

LIMITATIONS:

The study had several limitations. The sample size and the limited number of events precluded comparative subanalyses, as well as a more detailed stratification for preoperative chemotherapy regimens. Information about patients’ race and the presence of BRCA germline mutations, both of which seem to be relevant to the chance of achieving a major pathologic response, was not collected or available.

DISCLOSURES:

No specific funding was noted. Several coauthors have industry relationships outside of the submitted work.

A version of this article first appeared on Medscape.com.

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

Patients with treatment-refractory cancers who did not meet eligibility criteria for a pan-cancer clinical trial but received waivers allowing them to participate had similar outcomes to patients who participated without waivers, a new analysis revealed.

The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.

“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”

Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.

In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.

In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.

Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing. 

The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers. 

Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.

A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.

The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).

“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.

The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.

So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.

Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.

Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”

However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.

“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”

Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
 

A version of this article appeared on Medscape.com.

Patients with treatment-refractory cancers who did not meet eligibility criteria for a pan-cancer clinical trial but received waivers allowing them to participate had similar outcomes to patients who participated without waivers, a new analysis revealed.

The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.

“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”

Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.

In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.

In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.

Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing. 

The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers. 

Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.

A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.

The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).

“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.

The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.

So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.

Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.

Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”

However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.

“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”

Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
 

A version of this article appeared on Medscape.com.

Patients with treatment-refractory cancers who did not meet eligibility criteria for a pan-cancer clinical trial but received waivers allowing them to participate had similar outcomes to patients who participated without waivers, a new analysis revealed.

The study, published online in Clinical Cancer Research, highlighted the potential benefits of broadening eligibility criteria for clinical trials.

“It is well known that results in an ‘ideal’ population do not always translate to the real-world population,” senior author Hans Gelderblom, MD, chair of the Department of Medical Oncology at the Leiden University Medical Center, Leiden, the Netherlands, said in a press release. “Eligibility criteria are often too strict, and educated exemptions by experienced investigators can help individual patients, especially in a last-resort trial.”

Although experts have expressed interest in improving trial inclusivity, it’s unclear how doing so might impact treatment safety and efficacy.

In the Drug Rediscovery Protocol (DRUP), Dr. Gelderblom and colleagues examined the impact of broadening trial eligibility on patient outcomes. DRUP is an ongoing Dutch national, multicenter, pan-cancer, nonrandomized clinical trial in which patients are treated off-label with approved molecularly targeted or immunotherapies.

In the trial, 1019 patients with treatment-refractory disease were matched to one of the available study drugs based on their tumor molecular profile and enrolled in parallel cohorts. Cohorts were defined by tumor type, molecular profile, and study drug.

Among these patients, 82 patients — 8% of the cohort — were granted waivers to participate. Most waivers (45%) were granted as exceptions to general- or drug-related eligibility criteria, often because of out-of-range lab results. Other categories included treatment and testing exceptions, as well as out-of-window testing. 

The researchers then compared safety and efficacy outcomes between the 82 participants granted waivers and the 937 who did not receive waivers. 

Overall, Dr. Gelderblom’s team found that the rate of serious adverse events was similar between patients who received a waiver and those who did not: 39% vs 41%, respectively.

A relationship between waivers and serious adverse events was deemed “unlikely” for 86% of patients and “possible” for 14%. In two cases concerning a direct relationship, for instance, patients who received waivers for decreased hemoglobin levels developed anemia.

The rate of clinical benefit — defined as an objective response or stable disease for at least 16 weeks — was similar between the groups. Overall, 40% of patients who received a waiver (33 of 82) had a clinical benefit vs 33% of patients without a waiver (P = .43). Median overall survival for patients that received a waiver was also similar — 11 months in the waiver group and 8 months in the nonwaiver group (hazard ratio, 0.87; P = .33).

“Safety and clinical benefit were preserved in patients for whom a waiver was granted,” the authors concluded.

The study had several limitations. The diversity of cancer types, treatments, and reasons for protocol exemptions precluded subgroup analyses. In addition, because the decision to grant waivers depended in large part on the likelihood of clinical benefit, “it is possible that patients who received waivers were positively selected for clinical benefit compared with the general study population,” the authors wrote.

So, “although the clinical benefit rate of the patient group for whom a waiver was granted appears to be slightly higher, this difference might be explained by the selection process of the central study team, in which each waiver request was carefully considered, weighing the risks and potential benefits for the patient in question,” the authors explained.

Overall, “these findings advocate for a broader and more inclusive design when establishing novel trials, paving the way for a more effective and tailored application of cancer therapies in patients with advanced or refractory disease,” Dr. Gelderblom said.

Commenting on the study, Bishal Gyawali, MD, PhD, said that “relaxing eligibility criteria is important, and I support this. Trials should include patients that are more representative of the real-world, so that results are generalizable.”

However, “the paper overemphasized efficacy,” said Dr. Gyawali, from Queen’s University, Kingston, Ontario, Canada. The sample size of waiver-granted patients was small, plus “the clinical benefit rate is not a marker of efficacy.

“The response rate is somewhat better, but for a heterogeneous study with multiple targets and drugs, it is difficult to say much about treatment effects here,” Dr. Gyawali added. Overall, “we shouldn’t read too much into treatment benefits based on these numbers.”

Funding for the study was provided by the Stelvio for Life Foundation, the Dutch Cancer Society, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, pharma&, Eisai Co., Ipsen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. Dr. Gelderblom declared no conflicts of interest, and Dr. Gyawali declared no conflicts of interest related to his comment.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with fair or worse bowel preparation have lower adenoma detection rates and a higher risk for postcolonoscopy colorectal cancer (PCCRC) death, new data showed.

METHODOLOGY:

• Few large studies have investigated the degree of bowel preparation with long-term colorectal cancer (CRC) outcomes.
• Researchers analyzed data from 335,466 individuals aged 50 years and older who underwent screening colonoscopy in Austria over 10 years (2012-2022).
• Bowel preparation quality was assessed using the five-point Aronchick scale and categorized as excellent, good, fair, poor, or inadequate.
• Logistic regression and time-to-event analyses were used to assess the impact of bowel preparation quality on adenoma detection and PCCRC mortality.

TAKEAWAY:

• Bowel prep was excellent in 37% of procedures, good in 48%, fair in 11%, poor in 3%, and inadequate in 1%.
• With worsening degrees of bowel prep, the odds of detecting an adenoma, high-risk polyp, sessile serrated lesion (SSL), or traditional serrated adenoma (TSA) decreased significantly.
• For patients with inadequate bowel preparation, the odds ratio for detection was 0.44 for adenomas and 0.53 for SSL or TSA.
• The risk of dying from PCCRC was more than twofold higher with fair or poor bowel prep and more than fourfold higher with inadequate prep.
• Cumulative 10-year CRC mortality was 0.14% for excellent/good bowel preparation vs 0.41% for fair or worse preparation.

IN PRACTICE:

“Our findings further support the evidence that bowel preparation is a crucial element of high-quality colonoscopy that affects CRC outcomes in screening participants. Efforts should be made to increase bowel cleansing above fair scores,” the authors concluded.

SOURCE:

The study, led by Jasmin Zessner-Spitzenberg, MD, from the Division of Gastroenterology and Hepatology at the Medical University of Vienna, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The researchers lacked data on CRC risk factors and information on surveillance colonoscopies, which could bias the results. Bowel preparation solutions and preferences of endoscopists, or whether split dosing was applied, were unknown, which limits insights into variations in preparation effectiveness.

DISCLOSURES:

The study was supported by the Main Association of Statutory Insurance Institutions, the Austrian Society of Gastroenterology and Hepatology, and the Austrian Cancer Aid. Dr. Zessner-Spitzenberg had no relevant disclosures. Other participating authors disclosed competing interests in the form of advisory roles, grant/research support, and speaker fees received from industry and academic institutions.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with fair or worse bowel preparation have lower adenoma detection rates and a higher risk for postcolonoscopy colorectal cancer (PCCRC) death, new data showed.

METHODOLOGY:

• Few large studies have investigated the degree of bowel preparation with long-term colorectal cancer (CRC) outcomes.
• Researchers analyzed data from 335,466 individuals aged 50 years and older who underwent screening colonoscopy in Austria over 10 years (2012-2022).
• Bowel preparation quality was assessed using the five-point Aronchick scale and categorized as excellent, good, fair, poor, or inadequate.
• Logistic regression and time-to-event analyses were used to assess the impact of bowel preparation quality on adenoma detection and PCCRC mortality.

TAKEAWAY:

• Bowel prep was excellent in 37% of procedures, good in 48%, fair in 11%, poor in 3%, and inadequate in 1%.
• With worsening degrees of bowel prep, the odds of detecting an adenoma, high-risk polyp, sessile serrated lesion (SSL), or traditional serrated adenoma (TSA) decreased significantly.
• For patients with inadequate bowel preparation, the odds ratio for detection was 0.44 for adenomas and 0.53 for SSL or TSA.
• The risk of dying from PCCRC was more than twofold higher with fair or poor bowel prep and more than fourfold higher with inadequate prep.
• Cumulative 10-year CRC mortality was 0.14% for excellent/good bowel preparation vs 0.41% for fair or worse preparation.

IN PRACTICE:

“Our findings further support the evidence that bowel preparation is a crucial element of high-quality colonoscopy that affects CRC outcomes in screening participants. Efforts should be made to increase bowel cleansing above fair scores,” the authors concluded.

SOURCE:

The study, led by Jasmin Zessner-Spitzenberg, MD, from the Division of Gastroenterology and Hepatology at the Medical University of Vienna, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The researchers lacked data on CRC risk factors and information on surveillance colonoscopies, which could bias the results. Bowel preparation solutions and preferences of endoscopists, or whether split dosing was applied, were unknown, which limits insights into variations in preparation effectiveness.

DISCLOSURES:

The study was supported by the Main Association of Statutory Insurance Institutions, the Austrian Society of Gastroenterology and Hepatology, and the Austrian Cancer Aid. Dr. Zessner-Spitzenberg had no relevant disclosures. Other participating authors disclosed competing interests in the form of advisory roles, grant/research support, and speaker fees received from industry and academic institutions.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Individuals with fair or worse bowel preparation have lower adenoma detection rates and a higher risk for postcolonoscopy colorectal cancer (PCCRC) death, new data showed.

METHODOLOGY:

• Few large studies have investigated the degree of bowel preparation with long-term colorectal cancer (CRC) outcomes.
• Researchers analyzed data from 335,466 individuals aged 50 years and older who underwent screening colonoscopy in Austria over 10 years (2012-2022).
• Bowel preparation quality was assessed using the five-point Aronchick scale and categorized as excellent, good, fair, poor, or inadequate.
• Logistic regression and time-to-event analyses were used to assess the impact of bowel preparation quality on adenoma detection and PCCRC mortality.

TAKEAWAY:

• Bowel prep was excellent in 37% of procedures, good in 48%, fair in 11%, poor in 3%, and inadequate in 1%.
• With worsening degrees of bowel prep, the odds of detecting an adenoma, high-risk polyp, sessile serrated lesion (SSL), or traditional serrated adenoma (TSA) decreased significantly.
• For patients with inadequate bowel preparation, the odds ratio for detection was 0.44 for adenomas and 0.53 for SSL or TSA.
• The risk of dying from PCCRC was more than twofold higher with fair or poor bowel prep and more than fourfold higher with inadequate prep.
• Cumulative 10-year CRC mortality was 0.14% for excellent/good bowel preparation vs 0.41% for fair or worse preparation.

IN PRACTICE:

“Our findings further support the evidence that bowel preparation is a crucial element of high-quality colonoscopy that affects CRC outcomes in screening participants. Efforts should be made to increase bowel cleansing above fair scores,” the authors concluded.

SOURCE:

The study, led by Jasmin Zessner-Spitzenberg, MD, from the Division of Gastroenterology and Hepatology at the Medical University of Vienna, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The researchers lacked data on CRC risk factors and information on surveillance colonoscopies, which could bias the results. Bowel preparation solutions and preferences of endoscopists, or whether split dosing was applied, were unknown, which limits insights into variations in preparation effectiveness.

DISCLOSURES:

The study was supported by the Main Association of Statutory Insurance Institutions, the Austrian Society of Gastroenterology and Hepatology, and the Austrian Cancer Aid. Dr. Zessner-Spitzenberg had no relevant disclosures. Other participating authors disclosed competing interests in the form of advisory roles, grant/research support, and speaker fees received from industry and academic institutions.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Hello. I’m Mark Lewis, director of gastrointestinal (GI) oncology at Intermountain Health in Utah. I’m speaking from the 2024 ASCO Annual Meeting in Chicago, where we’ve seen some interesting, new data in GI cancers.

If you allow me, I’d like to go in a craniocaudal fashion. It’s my anatomic mnemonic. I think that’s appropriate because our plenary session yesterday kicked off with some exciting data in esophageal cancer, specifically esophageal adenocarcinoma. 

This was the long-awaited ESOPEC trial. It’s a phase 3 study looking at perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel), a chemo triplet, vs the CROSS protocol, which is neoadjuvant chemoradiation with carboplatin and paclitaxel. The primary endpoint was overall survival, and at first blush, FLOT looked to be the true winner. There were some really remarkable milestones in this study, and I have some reservations about the FLOT arm that I’ll raise in just a second. 

The investigators are to be commended because in a truly deadly disease, they reported a 5-year overall survival in half of the patients who were receiving FLOT. That is truly commendable and really a milestone in our field. The reason I take a little bit of issue with the trial is that I still have some questions about methodology.

It wasn’t that long ago at ASCO GI that there was a really heated debate called “FLOT or Not” — not in this precise setting, but asking the question, do we think that patients with upper GI malignancy are even fit enough to handle a chemo triplet like FLOT? 

The reason I bring that up now in 2024 is that, to my surprise, and I think to many others’, there was a lower-than-expected completion rate of the patients in this trial who were receiving the CROSS regimen. The number of people who were able to complete that in full was about two-thirds, which compared with a historical control from a trial scheme that first emerged over a decade ago that used to be over 90% completion. I found that quite strange. 

I also think this trial suffers a little bit, and unavoidably, from the evolution of care that’s happened since it was first enrolling. Of course, I refer to adjuvant immunotherapy. Now, the real question is whether there is synergy between patients who receive radiation upfront and then adjuvant nivolumab, as per CheckMate 577. 

In her plenary discussion, I thought Dr. Karyn Goodman did a masterful job — I would encourage you to watch it on ASCO’s website —discussing how we can take all these data and reconcile them for optimal patient outcome. She ultimately suggested that we might deploy all four modalities in the management of these people. 

She proposed a paradigm with a PET-adapted, upfront induction chemotherapy, then moving to chemoradiation, then moving to surgery, and finally moving to immunotherapy. That is all four of the traditional arms of oncology. I find that really rather remarkable. Watch that space. This is a great trial with really remarkable survival data, but I’m not entirely convinced that the CROSS arm was given its due. 

Next up, I want to talk about pancreas cancer, which is something near and dear to my heart. It affects about one in four of my patients and it remains, unfortunately, a highly lethal disease. I think the top-line news from this meeting is that the KRAS mutation is druggable. I’m probably showing my age, but when I did my fellowship in 2009 through 2012, I was taught that KRAS was sort of the undruggable mutation par excellence. At this meeting, we’ve seen maturing data in regard to targeting KRAS G12C with both sotorasib and adagrasib. The disease control rates are astounding, at 80% and more, which is really remarkable. I wouldn’t have believed that even a few years ago. 

I’m even more excited about how we bring a rising tide that can lift all boats and apply this to other KRAS mutations, and not just KRAS G12C but all KRAS mutations. I think that’s coming, hopefully, with the pan-RAS inhibitors, because once that happens — if that happens; I’ll try not to be irrationally exuberant — that would take the traditional mutation found in almost all pancreas cancers and really make it its own Achilles heel. I think that could be such a huge leap forward. 

Another matter, however, that remains unresolved at this meeting is in the neoadjuvant setting with pancreatic ductal adenocarcinoma. There’s still equipoise, actually, between neoadjuvant gemcitabine, paclitaxel, and FOLFIRINOX. I thought that that was very well spelled out by some of our Dutch colleagues, who continue to do great work in a variety of cancers, including colorectal. 

Where I’d like to move next is colorectal cancer. Of course, immunotherapy remains a hot topic at all of these conferences. There were three different aspects of immunotherapy I’d like to highlight at this conference in regard to colon and rectal cancer. 

First, Dr. Heinz-Josef Lenz presented updated data from CheckMate 8HW, which looked at nivolumab and ipilimumab (nivo/ipi) vs chemotherapy in the first line for MSI-high or mismatch repair–deficient colon cancer. Once again, the data we’ve had now for several years at the 2-year mark are incredibly impressive. The 2-year progression-free survival (PFS) rates for nivo/ipi are above 70% and down at around 14% for chemo. 

What was impressive about this meeting is that Dr. Lenz presented PFS2, trying to determine the impact, if any, of subsequent therapy. What was going on here, which I think was ethically responsible by the investigators, was crossover. About two-thirds of the chemo arm crossed over to any form of immuno-oncology (IO), and just under a half crossed over to nivo and ipi. The PFS benefits continued with up-front IO. The way that Dr. Lenz phrased it is that you really never get the chance to win back the benefit that you would derive by giving immunotherapy first line to someone who has MSI-high or mismatch repair–deficient metastatic colon cancer. 

One thing that’s still not settled in my mind, though, is, does this really dethrone single-agent immunotherapy, such as pembrolizumab in KEYNOTE-177? What I’m really driving at is the ipilimumab. Is the juice worth the squeeze? Is the addition of an anti-CTLA4 agent worth the toxicity that we know comes along with that mechanism of action? Watch this space. 

I was also really interested in NEOPRISM-CRC, which looked at the role of immunotherapy in neoadjuvant down-staging of radiographically high-risk stage II or stage III colon cancer. Here, the investigators really make a strong case that, up front in these potentially respectable cases, not only should we know about mismatch repair deficiency but we should actually be interrogating further for tumor mutational burden (TMB). 

They had TMB-high patients. In fact, the median TMB was 42 mutations per megabase, with really impressive down-staging using three cycles of every-3-week pembrolizumab before surgery. Again, I really think we’re at an exciting time where, even for colon cancer that looks operable up front, we might actually have the opportunity to improve pathologic and clinical complete responses before and after surgery. 

Finally, I want to bring up what continues to amaze me. Two years ago, at ASCO 2022, we heard from Dr. Andrea Cercek and the Memorial Sloan Kettering group about the incredible experience they were having with neoadjuvant, or frankly, definitive dostarlimab in mismatch repair–deficient locally advanced rectal cancer. 

I remember being at the conference and there was simultaneous publication of that abstract in The New York Times because it was so remarkable. There was a 100% clinical complete response. The patients didn’t require radiation, they didn’t require chemotherapy, and they didn’t require surgery for locally advanced rectal cancer, provided there was this vulnerability of mismatch-repair deficiency. 

Now, 2 years later, Dr. Cercek and her group have updated those data with more than 40 patients, and again, a 100% clinical complete response, including mature, complete responses at over a year in about 20 patients. Again, we are really doing our rectal cancer patients a disservice if we’re not checking for mismatch-repair deficiency upfront, and especially if we’re not talking about them in multidisciplinary conferences. 

One of the things that absolutely blows my mind about rectal cancer is just how complicated it’s becoming. I think it is the standard of care to discuss these cases upfront with radiation oncology, surgical oncology, medical oncology, and pathology. 

Maybe the overarching message I would take from everything I’ve said today is that the oncologist without the pathologist is blind. It’s really a dyad, a partnership that guides optimal medical oncology care. As much as I love ASCO, I often wish we had more of our pathology colleagues here. I look forward to taking all the findings from this meeting back to the tumor board and really having a dynamic dialogue.

Dr. Lewis is director, Department of Gastrointestinal Oncology, Intermountain Health, Salt Lake City, Utah. He has disclosed no relevant financial relationships. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Hello. I’m Mark Lewis, director of gastrointestinal (GI) oncology at Intermountain Health in Utah. I’m speaking from the 2024 ASCO Annual Meeting in Chicago, where we’ve seen some interesting, new data in GI cancers.

If you allow me, I’d like to go in a craniocaudal fashion. It’s my anatomic mnemonic. I think that’s appropriate because our plenary session yesterday kicked off with some exciting data in esophageal cancer, specifically esophageal adenocarcinoma. 

This was the long-awaited ESOPEC trial. It’s a phase 3 study looking at perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel), a chemo triplet, vs the CROSS protocol, which is neoadjuvant chemoradiation with carboplatin and paclitaxel. The primary endpoint was overall survival, and at first blush, FLOT looked to be the true winner. There were some really remarkable milestones in this study, and I have some reservations about the FLOT arm that I’ll raise in just a second. 

The investigators are to be commended because in a truly deadly disease, they reported a 5-year overall survival in half of the patients who were receiving FLOT. That is truly commendable and really a milestone in our field. The reason I take a little bit of issue with the trial is that I still have some questions about methodology.

It wasn’t that long ago at ASCO GI that there was a really heated debate called “FLOT or Not” — not in this precise setting, but asking the question, do we think that patients with upper GI malignancy are even fit enough to handle a chemo triplet like FLOT? 

The reason I bring that up now in 2024 is that, to my surprise, and I think to many others’, there was a lower-than-expected completion rate of the patients in this trial who were receiving the CROSS regimen. The number of people who were able to complete that in full was about two-thirds, which compared with a historical control from a trial scheme that first emerged over a decade ago that used to be over 90% completion. I found that quite strange. 

I also think this trial suffers a little bit, and unavoidably, from the evolution of care that’s happened since it was first enrolling. Of course, I refer to adjuvant immunotherapy. Now, the real question is whether there is synergy between patients who receive radiation upfront and then adjuvant nivolumab, as per CheckMate 577. 

In her plenary discussion, I thought Dr. Karyn Goodman did a masterful job — I would encourage you to watch it on ASCO’s website —discussing how we can take all these data and reconcile them for optimal patient outcome. She ultimately suggested that we might deploy all four modalities in the management of these people. 

She proposed a paradigm with a PET-adapted, upfront induction chemotherapy, then moving to chemoradiation, then moving to surgery, and finally moving to immunotherapy. That is all four of the traditional arms of oncology. I find that really rather remarkable. Watch that space. This is a great trial with really remarkable survival data, but I’m not entirely convinced that the CROSS arm was given its due. 

Next up, I want to talk about pancreas cancer, which is something near and dear to my heart. It affects about one in four of my patients and it remains, unfortunately, a highly lethal disease. I think the top-line news from this meeting is that the KRAS mutation is druggable. I’m probably showing my age, but when I did my fellowship in 2009 through 2012, I was taught that KRAS was sort of the undruggable mutation par excellence. At this meeting, we’ve seen maturing data in regard to targeting KRAS G12C with both sotorasib and adagrasib. The disease control rates are astounding, at 80% and more, which is really remarkable. I wouldn’t have believed that even a few years ago. 

I’m even more excited about how we bring a rising tide that can lift all boats and apply this to other KRAS mutations, and not just KRAS G12C but all KRAS mutations. I think that’s coming, hopefully, with the pan-RAS inhibitors, because once that happens — if that happens; I’ll try not to be irrationally exuberant — that would take the traditional mutation found in almost all pancreas cancers and really make it its own Achilles heel. I think that could be such a huge leap forward. 

Another matter, however, that remains unresolved at this meeting is in the neoadjuvant setting with pancreatic ductal adenocarcinoma. There’s still equipoise, actually, between neoadjuvant gemcitabine, paclitaxel, and FOLFIRINOX. I thought that that was very well spelled out by some of our Dutch colleagues, who continue to do great work in a variety of cancers, including colorectal. 

Where I’d like to move next is colorectal cancer. Of course, immunotherapy remains a hot topic at all of these conferences. There were three different aspects of immunotherapy I’d like to highlight at this conference in regard to colon and rectal cancer. 

First, Dr. Heinz-Josef Lenz presented updated data from CheckMate 8HW, which looked at nivolumab and ipilimumab (nivo/ipi) vs chemotherapy in the first line for MSI-high or mismatch repair–deficient colon cancer. Once again, the data we’ve had now for several years at the 2-year mark are incredibly impressive. The 2-year progression-free survival (PFS) rates for nivo/ipi are above 70% and down at around 14% for chemo. 

What was impressive about this meeting is that Dr. Lenz presented PFS2, trying to determine the impact, if any, of subsequent therapy. What was going on here, which I think was ethically responsible by the investigators, was crossover. About two-thirds of the chemo arm crossed over to any form of immuno-oncology (IO), and just under a half crossed over to nivo and ipi. The PFS benefits continued with up-front IO. The way that Dr. Lenz phrased it is that you really never get the chance to win back the benefit that you would derive by giving immunotherapy first line to someone who has MSI-high or mismatch repair–deficient metastatic colon cancer. 

One thing that’s still not settled in my mind, though, is, does this really dethrone single-agent immunotherapy, such as pembrolizumab in KEYNOTE-177? What I’m really driving at is the ipilimumab. Is the juice worth the squeeze? Is the addition of an anti-CTLA4 agent worth the toxicity that we know comes along with that mechanism of action? Watch this space. 

I was also really interested in NEOPRISM-CRC, which looked at the role of immunotherapy in neoadjuvant down-staging of radiographically high-risk stage II or stage III colon cancer. Here, the investigators really make a strong case that, up front in these potentially respectable cases, not only should we know about mismatch repair deficiency but we should actually be interrogating further for tumor mutational burden (TMB). 

They had TMB-high patients. In fact, the median TMB was 42 mutations per megabase, with really impressive down-staging using three cycles of every-3-week pembrolizumab before surgery. Again, I really think we’re at an exciting time where, even for colon cancer that looks operable up front, we might actually have the opportunity to improve pathologic and clinical complete responses before and after surgery. 

Finally, I want to bring up what continues to amaze me. Two years ago, at ASCO 2022, we heard from Dr. Andrea Cercek and the Memorial Sloan Kettering group about the incredible experience they were having with neoadjuvant, or frankly, definitive dostarlimab in mismatch repair–deficient locally advanced rectal cancer. 

I remember being at the conference and there was simultaneous publication of that abstract in The New York Times because it was so remarkable. There was a 100% clinical complete response. The patients didn’t require radiation, they didn’t require chemotherapy, and they didn’t require surgery for locally advanced rectal cancer, provided there was this vulnerability of mismatch-repair deficiency. 

Now, 2 years later, Dr. Cercek and her group have updated those data with more than 40 patients, and again, a 100% clinical complete response, including mature, complete responses at over a year in about 20 patients. Again, we are really doing our rectal cancer patients a disservice if we’re not checking for mismatch-repair deficiency upfront, and especially if we’re not talking about them in multidisciplinary conferences. 

One of the things that absolutely blows my mind about rectal cancer is just how complicated it’s becoming. I think it is the standard of care to discuss these cases upfront with radiation oncology, surgical oncology, medical oncology, and pathology. 

Maybe the overarching message I would take from everything I’ve said today is that the oncologist without the pathologist is blind. It’s really a dyad, a partnership that guides optimal medical oncology care. As much as I love ASCO, I often wish we had more of our pathology colleagues here. I look forward to taking all the findings from this meeting back to the tumor board and really having a dynamic dialogue.

Dr. Lewis is director, Department of Gastrointestinal Oncology, Intermountain Health, Salt Lake City, Utah. He has disclosed no relevant financial relationships. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Hello. I’m Mark Lewis, director of gastrointestinal (GI) oncology at Intermountain Health in Utah. I’m speaking from the 2024 ASCO Annual Meeting in Chicago, where we’ve seen some interesting, new data in GI cancers.

If you allow me, I’d like to go in a craniocaudal fashion. It’s my anatomic mnemonic. I think that’s appropriate because our plenary session yesterday kicked off with some exciting data in esophageal cancer, specifically esophageal adenocarcinoma. 

This was the long-awaited ESOPEC trial. It’s a phase 3 study looking at perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel), a chemo triplet, vs the CROSS protocol, which is neoadjuvant chemoradiation with carboplatin and paclitaxel. The primary endpoint was overall survival, and at first blush, FLOT looked to be the true winner. There were some really remarkable milestones in this study, and I have some reservations about the FLOT arm that I’ll raise in just a second. 

The investigators are to be commended because in a truly deadly disease, they reported a 5-year overall survival in half of the patients who were receiving FLOT. That is truly commendable and really a milestone in our field. The reason I take a little bit of issue with the trial is that I still have some questions about methodology.

It wasn’t that long ago at ASCO GI that there was a really heated debate called “FLOT or Not” — not in this precise setting, but asking the question, do we think that patients with upper GI malignancy are even fit enough to handle a chemo triplet like FLOT? 

The reason I bring that up now in 2024 is that, to my surprise, and I think to many others’, there was a lower-than-expected completion rate of the patients in this trial who were receiving the CROSS regimen. The number of people who were able to complete that in full was about two-thirds, which compared with a historical control from a trial scheme that first emerged over a decade ago that used to be over 90% completion. I found that quite strange. 

I also think this trial suffers a little bit, and unavoidably, from the evolution of care that’s happened since it was first enrolling. Of course, I refer to adjuvant immunotherapy. Now, the real question is whether there is synergy between patients who receive radiation upfront and then adjuvant nivolumab, as per CheckMate 577. 

In her plenary discussion, I thought Dr. Karyn Goodman did a masterful job — I would encourage you to watch it on ASCO’s website —discussing how we can take all these data and reconcile them for optimal patient outcome. She ultimately suggested that we might deploy all four modalities in the management of these people. 

She proposed a paradigm with a PET-adapted, upfront induction chemotherapy, then moving to chemoradiation, then moving to surgery, and finally moving to immunotherapy. That is all four of the traditional arms of oncology. I find that really rather remarkable. Watch that space. This is a great trial with really remarkable survival data, but I’m not entirely convinced that the CROSS arm was given its due. 

Next up, I want to talk about pancreas cancer, which is something near and dear to my heart. It affects about one in four of my patients and it remains, unfortunately, a highly lethal disease. I think the top-line news from this meeting is that the KRAS mutation is druggable. I’m probably showing my age, but when I did my fellowship in 2009 through 2012, I was taught that KRAS was sort of the undruggable mutation par excellence. At this meeting, we’ve seen maturing data in regard to targeting KRAS G12C with both sotorasib and adagrasib. The disease control rates are astounding, at 80% and more, which is really remarkable. I wouldn’t have believed that even a few years ago. 

I’m even more excited about how we bring a rising tide that can lift all boats and apply this to other KRAS mutations, and not just KRAS G12C but all KRAS mutations. I think that’s coming, hopefully, with the pan-RAS inhibitors, because once that happens — if that happens; I’ll try not to be irrationally exuberant — that would take the traditional mutation found in almost all pancreas cancers and really make it its own Achilles heel. I think that could be such a huge leap forward. 

Another matter, however, that remains unresolved at this meeting is in the neoadjuvant setting with pancreatic ductal adenocarcinoma. There’s still equipoise, actually, between neoadjuvant gemcitabine, paclitaxel, and FOLFIRINOX. I thought that that was very well spelled out by some of our Dutch colleagues, who continue to do great work in a variety of cancers, including colorectal. 

Where I’d like to move next is colorectal cancer. Of course, immunotherapy remains a hot topic at all of these conferences. There were three different aspects of immunotherapy I’d like to highlight at this conference in regard to colon and rectal cancer. 

First, Dr. Heinz-Josef Lenz presented updated data from CheckMate 8HW, which looked at nivolumab and ipilimumab (nivo/ipi) vs chemotherapy in the first line for MSI-high or mismatch repair–deficient colon cancer. Once again, the data we’ve had now for several years at the 2-year mark are incredibly impressive. The 2-year progression-free survival (PFS) rates for nivo/ipi are above 70% and down at around 14% for chemo. 

What was impressive about this meeting is that Dr. Lenz presented PFS2, trying to determine the impact, if any, of subsequent therapy. What was going on here, which I think was ethically responsible by the investigators, was crossover. About two-thirds of the chemo arm crossed over to any form of immuno-oncology (IO), and just under a half crossed over to nivo and ipi. The PFS benefits continued with up-front IO. The way that Dr. Lenz phrased it is that you really never get the chance to win back the benefit that you would derive by giving immunotherapy first line to someone who has MSI-high or mismatch repair–deficient metastatic colon cancer. 

One thing that’s still not settled in my mind, though, is, does this really dethrone single-agent immunotherapy, such as pembrolizumab in KEYNOTE-177? What I’m really driving at is the ipilimumab. Is the juice worth the squeeze? Is the addition of an anti-CTLA4 agent worth the toxicity that we know comes along with that mechanism of action? Watch this space. 

I was also really interested in NEOPRISM-CRC, which looked at the role of immunotherapy in neoadjuvant down-staging of radiographically high-risk stage II or stage III colon cancer. Here, the investigators really make a strong case that, up front in these potentially respectable cases, not only should we know about mismatch repair deficiency but we should actually be interrogating further for tumor mutational burden (TMB). 

They had TMB-high patients. In fact, the median TMB was 42 mutations per megabase, with really impressive down-staging using three cycles of every-3-week pembrolizumab before surgery. Again, I really think we’re at an exciting time where, even for colon cancer that looks operable up front, we might actually have the opportunity to improve pathologic and clinical complete responses before and after surgery. 

Finally, I want to bring up what continues to amaze me. Two years ago, at ASCO 2022, we heard from Dr. Andrea Cercek and the Memorial Sloan Kettering group about the incredible experience they were having with neoadjuvant, or frankly, definitive dostarlimab in mismatch repair–deficient locally advanced rectal cancer. 

I remember being at the conference and there was simultaneous publication of that abstract in The New York Times because it was so remarkable. There was a 100% clinical complete response. The patients didn’t require radiation, they didn’t require chemotherapy, and they didn’t require surgery for locally advanced rectal cancer, provided there was this vulnerability of mismatch-repair deficiency. 

Now, 2 years later, Dr. Cercek and her group have updated those data with more than 40 patients, and again, a 100% clinical complete response, including mature, complete responses at over a year in about 20 patients. Again, we are really doing our rectal cancer patients a disservice if we’re not checking for mismatch-repair deficiency upfront, and especially if we’re not talking about them in multidisciplinary conferences. 

One of the things that absolutely blows my mind about rectal cancer is just how complicated it’s becoming. I think it is the standard of care to discuss these cases upfront with radiation oncology, surgical oncology, medical oncology, and pathology. 

Maybe the overarching message I would take from everything I’ve said today is that the oncologist without the pathologist is blind. It’s really a dyad, a partnership that guides optimal medical oncology care. As much as I love ASCO, I often wish we had more of our pathology colleagues here. I look forward to taking all the findings from this meeting back to the tumor board and really having a dynamic dialogue.

Dr. Lewis is director, Department of Gastrointestinal Oncology, Intermountain Health, Salt Lake City, Utah. He has disclosed no relevant financial relationships. 

A version of this article appeared on Medscape.com.